title: IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes.
abstract: BACKGROUND
  Several lines of evidence suggest a dichotomy between immune active and quiescent cancers, with the former associated with a good prognostic phenotype and better responsiveness to immunotherapy. Central to such dichotomy is the master regulator of the acute inflammatory process interferon regulatory factor (IRF)-1. However, it remains unknown whether the responsiveness of IRF-1 to cytokines is able to differentiate cancer immune phenotypes.
  
  
  METHODS
  IRF-1 activation was measured in 15 melanoma cell lines at basal level and after treatment with IFN-γ, TNF-α and a combination of both. Microarray analysis was used to compare transcriptional patterns between cell lines characterised by high or low IRF-1 activation.
  
  
  RESULTS
  We observed a strong positive correlation between IRF-1 activation at basal level and after IFN-γ and TNF-α treatment. Microarray demonstrated that three cell lines with low and three with high IRF-1 inducible translocation scores differed in the expression of 597 transcripts. Functional interpretation analysis showed mTOR and Wnt/β-cathenin as the top downregulated pathways in the cell lines with low inducible IRF-1 activation, suggesting that a low IRF-1 inducibility recapitulates a cancer phenotype already described in literature characterised by poor prognosis.
  
  
  CONCLUSIONS
  Our findings support the central role of IRF-1 in influencing different tumour phenotypes.
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: D
authors.initials: D
authors.lastname: Murtas
authors.forename: D
authors.initials: D
authors.lastname: Maric
authors.forename: V
authors.initials: V
authors.lastname: De Giorgi
authors.forename: J
authors.initials: J
authors.lastname: Reinboth
authors.forename: A
authors.initials: A
authors.lastname: Worschech
authors.forename: P
authors.initials: P
authors.lastname: Fetsch
authors.forename: A
authors.initials: A
authors.lastname: Filie
authors.forename: M L
authors.initials: ML
authors.lastname: Ascierto
authors.forename: D
authors.initials: D
authors.lastname: Bedognetti
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Uccellini
authors.forename: L
authors.initials: L
authors.lastname: Chouchane
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: F M
authors.initials: FM
authors.lastname: Marincola
authors.forename: S
authors.initials: S
authors.lastname: Tomei
mesh_terms: D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006801:Humans; D007167:Immunotherapy; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D016328:NF-kappa B / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin; D007371:Interferon-gamma; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases